DESCRIPTION: The Family Smoking Prevention and Tobacco Control Act provides a unique opportunity for the FDA to affect an enormous improvement in public health. Granted the authority to regulate levels of nicotine, the key addictive agent in tobacco products, the FDA is i a position to help solve the problem of tobacco smoking, the leading contributor to preventable death and disease in the U.S. with an annual death toll of >400,000 individuals. Despite previous success in reducing the prevalence of smoking nationally, tobacco smoking has stabilized at about 19% of the adult population. Of even greater concern, young adults (18-25 years old) are the age group with the highest smoking prevalence in the U.S., at 34%. In order for the FDA to meet its stated priority of reducing addiction to tobacco products, there are a number of crucial scientific questions that must be answered. Specifically, the FDA must be provided with data necessary to determine (1) the optimal level of nicotine yield in a cigarette to reduce smoking and tobacco dependence while still alleviating nicotine craving and withdrawal, and (2) how reduction to different nicotine yields would affect large subpopulations of smokers and possibly produce unintended consequences. It is vital that the FDA has comprehensive information available to support the goal of reducing nicotine yield. While some literature has documented behavioral responses to cigarettes of various nicotine yields, very little research is available to document cognitive and neural responses to reduced-nicotine cigarettes. Even less of this information is available in young adults, the age group most likely to be affected by nicotine reduction strategies. The goal of this project is to advance tobacco regulatory science by testing the effects of reduced nicotine-yield cigarettes in young adult (18-25 years old) smokers. Using a within-subjects, counterbalanced design, the proposed study will therefore characterize the effects of smoking research cigarettes with varying nicotine yields (<0.05, 0.1, 0.282, or 0.68 mg nicotine) as compared with the participant's preferred-brand cigarette as the first cigarette of the day. Participants will be young (18-25 years old) adult daily smokers, teste following overnight abstinence. Self-reports of how they evaluate the experience of smoking the different cigarettes, including satisfaction, liking, relief of craving, and nicotine withdrawal wil be obtained. Also measured will be how the cigarettes affect the ability to sustain attention, a cognitive function that is impaired in abstinent smokers. Functional magnetic resonance imaging (fMRI) will be used to provide a brain biomarker of the response to the different nicotine yields which can further inform understanding of the subjective and cognitive effects. This work will provide novel, critical data to guide tobacco regulatory policy, will advance the field of tobacco regulatory science, and will establish innovative scientific methodology for future evaluation of tobacco products from a regulatory perspective.